The effects of exposure to crude oil or PAHs on fish swim bladder development and function.

The failure of the swim bladder to inflate during fish development is a common and sensitive response to exposure to petrochemicals. Here, we review potential mechanisms by which petrochemicals or their toxic components (polycyclic aromatic hydrocarbons; PAHs) may affect swim bladder inflation, particularly during early life stages. Surface films formed by oil can cause a physical barrier to primary inflation by air gulping, and are likely important during oil spills. The act of swimming to the surface for primary inflation can be arduous for some species, and may prevent inflation if this behavior is limited by toxic effects on vision or musculature. Some studies have noted altered gene expression in the swim bladder in response to PAHs, and Cytochrome P450 1A (CYP1A) can be induced in swim bladder or rete mirabile tissue, suggesting that PAHs can have direct effects on swim bladder development. Swim bladder inflation failure can also occur secondarily to the failure of other systems; cardiovascular impairment is the best elucidated of these mechanisms, but other mechanisms might include non-inflation as a sequela of disruption to thyroid signaling or cholesterol metabolism. Failed swim bladder inflation has the potential to lead to chronic sublethal effects that are as yet unstudied.

Prenatal exposure to polycyclic aromatic hydrocarbons modifies the effects of early life stress on attention and Thought Problems in late childhood.

BACKGROUND: Risk for childhood psychopathology is complex and multifactorial, implicating direct and interacting effects of familial and environmental factors. The role of environmental neurotoxicants in psychiatric risk is of growing concern, including polycyclic aromatic hydrocarbons (PAH), common in air pollution. Prenatal PAH exposure is linked to adverse physical, behavioral, and cognitive outcomes as well as increasing psychiatric risk. It is unclear whether environmental exposures, like PAH, magnify the effects of exposure to early life stress (ELS), a critical risk factor for psychopathology. The current work aimed to test potential interactions between prenatal PAH exposure and psychosocial/socioeconomic stress on psychiatric symptoms in school-age children. METHODS: Data were from the Columbia Center for Children's Environmental Health Mothers and Newborns longitudinal birth cohort study. Prenatal PAH exposure was ascertained though air monitoring during pregnancy and maternal PAH-DNA adducts at delivery. Mothers reported on ELS (child age 5) and on child psychiatric symptoms across childhood (child age 5, 7, 9, and 11) using the Child Behavior Checklist (CBCL). RESULTS: Significant prenatal airborne PAH × ELS interactions (FDR-corrected) predicted CBCL Attention (ß = 0.22, t(307) = 3.47, p < .001, pfdr  = .003) and Thought Problems T-scores (ß = 0.21, t(307) = 3.29, p = .001, pfdr  = .004) at age 11 (n = 319). Relative to those with lower exposure, children with higher prenatal PAH exposure exhibited stronger positive associations between ELS and CBCL Attention and Thought Problem T-scores. This interaction was also significant examining convergent ADHD measures (Conners, DuPaul) and examining maternal PAH-DNA adducts (ß = 0.29, t(261) = 2.48, p = .01; n = 273). A three-way interaction with assessment wave indicated that the PAH × ELS interaction on Attention Problems was stronger later in development (ß = 0.03, t(1,601) = 2.19, p = .03; n = 477). CONCLUSIONS: Prenatal exposure to PAH, a common neurotoxicant in air pollution, may magnify or sustain the effects of early life psychosocial/socioeconomic stress on psychiatric outcomes later in child development. This work highlights the critical role of air pollution exposure on child mental health.

[The relationship between histone H3Ser10 phosphorylation and DNA damage in periphery blood lymphocytes of polycyclic aromatic hydrocarbons exposed workers].

Objective: To investigate the effect of polycyclic aromatic hydrocarbons (PAHs) exposure on the level of histone H3Ser10 phosphorylation (p-H3S10) and DNA damage degree in peripheral blood lymphocyte (PBLCs). Method: 75 coke oven workers from Benxi steel plant in Liaoning Province of China (PAHs-exposed group) and local 50 hot rolling workers (control group) were recruited in this study with age, working years, labor intensity and high temperature for matching factors using cluster sampling method in 2014. HPLC-fluorescence was performed to determine the level of urinary 1-hydroxypyrene (1-OHP), DNA damage and specific histone modification were measured in PBLCs of the subjects through comet assay and ELISA assay, respectively. Linear regression model analysis was used to analyze the differences among PAHs exposure, DNA damage and p-H3S10 level in two groups. The Mediation analysis was used to analyze the regulated relationships between urinary 1-OHP, DNA damage and histone modification through the bootstrap method. Results: Age of the control and the exposed group were (45.32±8.32) and (43.87±5.67) years old (P=0.284). The concentration of urinary 1-OHP, OTM value, Tail DNA% and p-H3S10 level in exposure group were higher than that in control group, while the M (P(5)-P(95)) of p-H3S10 levels in control and exposed group were 2.21 (0.68-4.71), 4.54 (1.85-23.91) (P<0.001). The degree p-H3S10 level was increased after the subgroups which were (2.59±1.19)%, (3.24±2.81)%, (5.55±3.25)%, (8.77±7.84)%, respectively, divided by quantitated 1-OHP concentration as P(0)-P(25), P(26)-P(50), P(51)-P(75) and P(76)-P(100) (P<0.001). We also found the correlations between urinary 1-OHP and p-H3S10 level or OTM value or Tail DNA%, ß (95%CI) were 0.264 (0.167-0.360), 0.500 (0.299-0.702), and 0.510 (0.384-0.671), respectively (P<0.001). Similar result was also observed between p-H3S10 level and OTM value or Tail DNA%, ß (95%CI) were 0.149 (0.073-0.226) and 0.220 (0.132-0.308) (P<0.001). Moreover, the mediation effect value of DNA damage on PAHs induced p-H3S10 alteration was 0.054(P=0.040). Conclusion: The results suggested that PAHs exposure could induce DNA damage and an increase in histone H3Ser10 phosphorylation in PBLCs. Particularly, the alteration of H3S10 phosphorylation may play an important role in regulating cell DNA damage repair.

Identification of risk factors in epidemiologic study based on ROC curve and network.

This article proposes a new non-parametric approach for identification of risk factors and their correlations in epidemiologic study, in which investigation data may have high variations because of individual differences or correlated risk factors. First, based on classification information of high or low disease incidence, we estimate Receptor Operating Characteristic (ROC) curve of each risk factor. Then, through the difference between ROC curve of each factor and diagonal, we evaluate and screen for the important risk factors. In addition, based on the difference of ROC curves corresponding to any pair of factors, we define a new type of correlation matrix to measure their correlations with disease, and then use this matrix as adjacency matrix to construct a network as a visualization tool for exploring the structure among factors, which can be used to direct further studies. Finally, these methods are applied to analysis on water pollutants and gastrointestinal tumor, and analysis on gene expression data in tumor and normal colon tissue samples.

Occupational syncarcinogenesis in the skin - combined effects of two carcinogens from the German occupational disease list.

BACKGROUND: Though scientifically undisputed, cutaneous syncarcinogenesis is not reflected in German occupational disease (OD) regulations, which tend to be guided by the tenet of monocausality. Recognition of nonmelanoma skin cancer (NMSC) and its precursor lesions as OD requires individual assessment as to whether the requirements pursuant to either OD 5103 (occupational exposure to natural UV radiation) or OD 5102 (occupational exposure to polycyclic aromatic hydrocarbons) are fulfilled. METHODS: Retrospective analysis of 28 patients (median age 72.5 years) with NMSC and respective precursor lesions who had been occupationally exposed to natural UV radiation and polycyclic aromatic hydrocarbons. All cases had undergone expert medical assessment between September 2012 and September 2015. RESULTS: According to our assessments, all 28 cases met the occupational requirements pursuant to OD 5103 and 5102. In 26 cases (93 %), we recommended recognition of skin cancer as occupational disease pursuant to both OD 5103 and OD 5102. The competent occupational insurance association (BG) followed our recommendation in four cases. In eight cases, recognition was solely based on OD 5103; in ten cases, only on OD 5102. Four cases were denied recognition. CONCLUSIONS: Following adequate cumulative occupational exposure to natural UV light as well as occupational exposure to polycyclic aromatic hydrocarbons, NMSC or its precursor lesions arising in UV-exposed areas should be reported to the competent occupational insurance association as "OD 5103 and 5102 in terms of syncarcinogenesis". Apart from the fact that the ensuing recognition proceedings will be able to more adequately reflect real-life workplace conditions, filing a report pursuant to both ODs also allows for recognition of basal cell carcinoma as occupational disease. According to current regulations, this would not be possible, if the assessment were solely based on OD 5103.

Effects of prenatal exposure to air pollutants (polycyclic aromatic hydrocarbons) on the development of brain white matter, cognition, and behavior in later childhood.

IMPORTANCE: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and neurotoxic environmental contaminants. Prenatal PAH exposure is associated with subsequent cognitive and behavioral disturbances in childhood. OBJECTIVES: To identify the effects of prenatal PAH exposure on brain structure and to assess the cognitive and behavioral correlates of those abnormalities in school-age children. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional imaging study in a representative community-based cohort followed up prospectively from the fetal period to ages 7 to 9 years. The setting was urban community residences and an academic imaging center. Participants included a sample of 40 minority urban youth born to Latina (Dominican) or African American women. They were recruited between February 2, 1998, and March 17, 2006. MAIN OUTCOMES AND MEASURES: Morphological measures that index local volumes of the surface of the brain and of the white matter surface after cortical gray matter was removed. RESULTS: We detected a dose-response relationship between increased prenatal PAH exposure (measured in the third trimester but thought to index exposure for all of gestation) and reductions of the white matter surface in later childhood that were confined almost exclusively to the left hemisphere of the brain and that involved almost its entire surface. Reduced left hemisphere white matter was associated with slower information processing speed during intelligence testing and with more severe externalizing behavioral problems, including attention-deficit/hyperactivity disorder symptoms and conduct disorder problems. The magnitude of left hemisphere white matter disturbances mediated the significant association of PAH exposure with slower processing speed. In addition, measures of postnatal PAH exposure correlated with white matter surface measures in dorsal prefrontal regions bilaterally when controlling for prenatal PAH. CONCLUSIONS AND RELEVANCE: Our findings suggest that prenatal exposure to PAH air pollutants contributes to slower processing speed, attention-deficit/hyperactivity disorder symptoms, and externalizing problems in urban youth by disrupting the development of left hemisphere white matter, whereas postnatal PAH exposure contributes to additional disturbances in the development of white matter in dorsal prefrontal regions.

A study of the status of exposure to polycyclic aromatic hydrocarbons (PAHs) in relation to its metabolites among workers in a Korean chemical factory / Um estudo sobre o estado de exposição a hidrocarbonetos aromáticos policíclicos (HAPs), em relação aos seus metabolitos, entre os trabalhadores em fábricas de produtos químicos coreana

The study was conducted to evaluate the status of worker exposure to polycyclic aromatic hydrocarbons (PAHs) through the measurement of urinary metabolites such as 1-hydroxypyrene (OHP) and 2-naphthol. A survey using a questionnaire involving 326 workers with measurement of urinary metabolites of 1-OHP and 2-naphthol was conducted. The differences in urinary 1-OHP and 2-naphthol concentrations, and changes in work, smoking habits and lifestyle were analyzed. The number of male subjects was 314 (96.3%), the largest age group was the fifth decade (170 cases, 52.1%). The urinary 1-OHP and 2-naphthol concentrations were significantly higher in the production workers. The urinary 1-OHP and 2-naphthol concentrations were significantly higher in smokers. In a multiple regression model, log (1-OHP) increased in smokers and production workers, while log (2-naphthol) only increased in smokers. Our results suggest that workers in this factory were exposed to PAHs from non-occupational as well as occupational sources. The occupational exposure to PAHs can be reduced through the improvement of the process, but the exposure due to smoking can be prevented only by giving up smoking.

O presente estudo foi realizado para avaliar o estado de exposição a hidrocarbonetos aromáticos policíclicos (HAPs) em trabalhadores, por medição de metabólitos urinários, tais como 1-hidroxipireno (OHP) e 2-naftol. Foi realizada uma pesquisa por questionário envolvendo 326 trabalhadores e a mensuração dos metabólitos urinários de 1-OHP e 2-naftol. Foram analisadas as diferenças na urinária 1-OHP e as concentrações de 2-naftol e mudanças pelo trabalho, hábito de fumar e estilo de vida. O número de indivíduos do sexo masculino foi de 314 (96,3%), a maior faixa etária foi a quinta década (170 casos, 52,1 %). Com relação aos metabólitos urinários 1 -OHP e 2-naftol, as concentrações foram significativamente maiores nos trabalhadores produtivos. As concentrações dos metabólitos urinários 1-OHP e 2-naftol foram significativamente maiores nos fumantes. Em um modelo de regressão múltipla, log (1-OHP) aumentou em fumantes e em trabalhadores produtivos, enquanto que log (2-naftol) aumentou apenas em fumantes. Nossos resultados sugerem que os trabalhadores desta fábrica foram expostos tanto a HAPs de fontes não ocupacionais como ocupacionais. A exposição ocupacional a HAPs pode ser diminuída através da melhoria do processo, mas a exposição devido ao fumo só pode ser impedida interrompendo esse hábito.

A study of the status of exposure to polycyclic aromatic hydrocarbons (PAHs) in relation to its metabolites among workers in a Korean chemical factory.

The study was conducted to evaluate the status of worker exposure to polycyclic aromatic hydrocarbons (PAHs) through the measurement of urinary metabolites such as 1-hydroxypyrene (OHP) and 2-naphthol. A survey using a questionnaire involving 326 workers with measurement of urinary metabolites of 1-OHP and 2-naphthol was conducted. The differences in urinary 1-OHP and 2-naphthol concentrations, and changes in work, smoking habits and lifestyle were analyzed. The number of male subjects was 314 (96.3%), the largest age group was the fifth decade (170 cases, 52.1%). The urinary 1-OHP and 2-naphthol concentrations were significantly higher in the production workers. The urinary 1-OHP and 2-naphthol concentrations were significantly higher in smokers. In a multiple regression model, log (1-OHP) increased in smokers and production workers, while log (2-naphthol) only increased in smokers. Our results suggest that workers in this factory were exposed to PAHs from non-occupational as well as occupational sources. The occupational exposure to PAHs can be reduced through the improvement of the process, but the exposure due to smoking can be prevented only by giving up smoking.

Polycyclic aromatic hydrocarbons in residential dust and risk of childhood acute lymphoblastic leukemia.

Several polycyclic aromatic hydrocarbons (PAHs) are known or probable human carcinogens. We evaluated the relationship between PAH exposure and risk of childhood acute lymphoblastic leukemia (ALL) using concentrations in residential dust as an exposure indicator. We conducted a population-based case-control study (251 ALL cases, 306 birth-certificate controls) in Northern and Central California from 2001 to 2007. We collected residential dust using a high volume small surface sampler (HVS3) (n=185 cases, 212 controls) or by sampling from participants' household vacuum cleaners (n=66 cases, 94 controls). We evaluated log-transformed concentrations of 9 individual PAHs, the summed PAHs, and the summed PAHs weighted by their carcinogenic potency (the toxic equivalence). We calculated odds ratios (ORs) and 95% confidence intervals (CI) using logistic regression adjusting for demographic characteristics and duration between diagnosis/reference date and dust collection. Among participants with HVS3 dust, risk of ALL was not associated with increasing concentration of any PAHs based on OR perln(ng/g). Among participants with vacuum dust, we observed positive associations between ALL risk and increasing concentrations of benzo[a]pyrene (OR perln[ng/g]=1.42, 95% CI=0.95, 2.12), dibenzo[a,h]anthracene (OR=1.98, 95% CI=1.11, 3.55), benzo[k]fluoranthene (OR=1.71, 95% CI=0.91, 3.22), indeno[1,2,3-cd]pyrene (OR=1.81, 95% CI=1.04, 3.16), and the toxic equivalence (OR=2.35, 95% CI=1.18, 4.69). The increased ALL risk among participants with vacuum dust suggests that PAH exposure may increase the risk of childhood ALL; however, reasons for the different results based on HVS3 dust samples deserve further study.

Lung cancer mortality and exposure to polycyclic aromatic hydrocarbons in British coke oven workers.

BACKGROUND: Workers on coke oven plants may be exposed to potentially carcinogenic polycyclic aromatic hydrocarbons (PAHs), particularly during work on the ovens tops. Two cohorts, employees of National Smokeless Fuels (NSF) and the British Steel Corporation (BSC) totalling more than 6,600 British coke plant workers employed in 1967, had been followed up to mid-1987 for mortality. Previous analyses suggested an excess in lung cancer risk of around 25%, or less when compared with Social Class IV ('partly skilled').Analyses based on internal comparisons within the cohorts identified statistical associations with estimates of individual exposures, up to the start of follow-up, to benzene-soluble materials (BSM), widely used as a metric for mixtures of PAHs. Some associations were also found with times spent in certain coke ovens jobs with specific exposure scenarios, but results were not consistent across the two cohorts and limitations in the exposure estimates were noted. The present study was designed to reanalyse the existing data on lung cancer mortality, incorporating revised and improved exposure estimates to BSM and to benzo[a]pyrene (B[a]P), including increments during the follow-up and a lag for latency. METHODS: Mean annual average concentrations of both BSM and B[a]P were estimated by analysis of variance (ANOVA) from concentration measurements at all NSF and six BSC plants, and summarised by job and plant, with a temporal trend (for the BSM only). These were combined with subjects' work histories, to produce exposure estimates in each year of follow-up, with a 10-year lag to allow for latency. Exposures to BSM and to B[a]P were sufficiently uncorrelated to permit analysis in relation to each variable separately.Lung cancer death risks during the follow-up were analysed in relation to the estimated time-dependent exposures, both continuous and grouped, using Cox regression models, with adjustment for age. RESULTS: Changing the exposure estimates changed the estimated relative risks compared with earlier results, but the new analyses showed no significant trends with continuous measures of exposure to either BSM or B[a]P, nor with time spent on ovens tops. Analyses with grouped exposures showed mixed results. Across all BSC plants, the relative risk coefficient for working 5 or more years on ovens tops, where the exposures were highest, was 1.81, which was statistically significant. However, results for those with 0-5 years on ovens tops did not suggest a trend; the evidence for an underlying relationship was thus suggestive but not strong. CONCLUSIONS: The new results are in line with previous findings; they show some signs consistent with an effect of coke ovens work on lung cancer risk, especially on ovens tops, but the preponderant absence of significant results, and the inconsistencies between results for NSF and BSC, highlight how little evidence there is in these data of any effect.

N-acetyltransferase 2 phenotype, occupation, and bladder cancer risk: results from the EPIC cohort.

BACKGROUND: An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case-control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. METHODS: Exposure to aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for 754 cases and 833 controls for whom occupational information was documented. A semiquantitative job-exposure matrix was applied to at-risk occupations to estimate the exposure as low, medium, or high based on tertiles of the distribution of the exposure score in controls. Using a comprehensive genotyping, NAT2 acetylation status could be categorized from 6-single-nucleotide polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA from archived blood samples. RESULTS: Occupational exposure to aromatic amines and PAH was associated with an increased bladder cancer risk [upper tertile of the distribution of the exposure score: OR = 1.37; 95% confidence interval (CI), 1.02-1.84, and OR = 1.50; 95% CI, 1.09-2.05, respectively]. NAT2 slow acetylation did not modify these risk estimates and was not itself associated with bladder cancer risk (OR = 1.02; 95% CI, 0.81-1.29). CONCLUSIONS: These findings confirm established or suspected occupational risk factors but not the anticipated role of NAT2 slow acetylation in bladder cancer. No interaction was detected between NAT2 and any exposure of interest, including smoking. IMPACT: Genetic testing for NAT2 would be inappropriate in occupational settings.

CYP1A1 genetic polymorphism and polycyclic aromatic hydrocarbons on pulmonary function in the elderly: haplotype-based approach for gene-environment interaction.

Lung function may be impaired by environmental pollutants not only acting alone, but working with genetic factors as well. Few epidemiologic studies have been conducted to explore the interplay of polycyclic aromatic hydrocarbons (PAHs) exposure and genetic polymorphism on lung function in the elderly. For genetic polymorphism, haplotype is considered a more informative unit than single nucleotide polymorphism markers. Therefore, we examined the role of haplotype based-CYP1A1 polymorphism in the effect of PAHs exposure on lung function in 422 participants from a community-based panel of elderly adults in Seoul, Korea. Linear mixed effect models were fit to evaluate the association of PAH exposure markers (urinary 1-hydroxypyrene and 2-naphthol) with FVC, FEV1, FEV1/FVC, and FEF25₋75, and then the interaction with CYP1A1 haplotype constructed from three single nucleotide polymorphisms of the gene (rs4646421/rs4646422/rs1048943). Urinary 1-hydroxypyrene levels were inversely associated with FEV1/FVC (p<0.05), whereas urinary 2-naphthol levels failed to show associations with lung function. Urinary 1-hydroxypyrene was significantly associated with decrease in FEV1/FVC among participants with rs4646421 variants (CT+TT), rs4646422 wild-type (GG), and rs1048943 wild-type (AA). At least one TGA haplotype predicted a 0.88% (95% confidence interval, 0.31-1.45%) reduction in FEV1/FVC with an interquartile range increase in 1-hydroxypyrene, whereas no relationship was observed in participants without TGA haplotype (p for interaction=0.045). Similar patterns were also observed in FEF25₋75. We did not find any main effects of CYP1A1 genetic polymorphisms on lung functions. Our findings suggest that PAH exposure producing 1-hydroxypyrene as a metabolite compromises lung function in the elderly, and that haplotype-based CYP1A1 polymorphism modifies the risk.

Mitochondrial DNA copy number and exposure to polycyclic aromatic hydrocarbons.

BACKGROUND: Increased mitochondrial DNA copy number (mtDNAcn) is a biologic response to mtDNA damage and dysfunction, predictive of lung cancer risk. Polycyclic aromatic hydrocarbons (PAHs) are established lung carcinogens and may cause mitochondrial toxicity. Whether PAH exposure and PAH-related nuclear DNA (nDNA) genotoxic effects are linked with increased mtDNAcn has never been evaluated. METHODS: We investigated the effect of chronic exposure to PAHs on mtDNAcn in peripheral blood lymphocytes (PBLs) of 46 Polish male noncurrent smoking coke-oven workers and 44 matched controls, who were part of a group of 94 study individuals examined in our previous work. Subjects' PAH exposure and genetic alterations were characterized through measures of internal dose (urinary 1-pyrenol), target dose [anti-benzo[a]pyrene diolepoxide (anti-BPDE)-DNA adduct], genetic instability (micronuclei and telomere length), and DNA methylation (p53 promoter) in PBLs. mtDNAcn (MT/S) was measured using a validated real-time PCR method. RESULTS: Workers with PAH exposure above the median value (>3 µmol 1-pyrenol/mol creatinine) showed higher mtDNAcn [geometric means (GM) of 1.06 (unadjusted) and 1.07 (age-adjusted)] compared with controls [GM 0.89 (unadjusted); 0.89 (age-adjusted); (P = 0.029 and 0.016)], as well as higher levels of genetic and chromosomal [i.e., anti-BPDE-DNA adducts (P < 0.001), micronuclei (P < 0.001), and telomere length (P = 0.053)] and epigenetic [i.e., p53 gene-specific promoter methylation (P < 0.001)] alterations in the nDNA. In the whole study population, unadjusted and age-adjusted mtDNAcn was positively correlated with 1-pyrenol (P = 0.043 and 0.032) and anti-BPDE-DNA adducts (P = 0.046 and 0.049). CONCLUSIONS: PAH exposure and PAH-related nDNA genotoxicity are associated with increased mtDNAcn. IMPACT: The present study is suggestive of potential roles of mtDNAcn in PAH-induced carcinogenesis.

CYP1A1 gene polymorphisms: modulator of genetic damage in coal-tar workers.

AIM: It is well known that polycyclic aromatic hydrocarbons (PAHs) such as benzo (a) pyrene have carcinogenic properties and may cause many types of cancers in human populations. Genetic susceptibility might be due to variation in genes encoding for carcinogen metabolizing enzymes, such as cytochrome P-450 (CYP450). Our study aimed to investigate the effect of genetic polymorphisms of CYP1A1 (m1 and m2) on genetic damage in 115 coal-tar workers exposed to PAHs in their work place. METHODS: Genetic polymorphisms of CYP1A1 were determined by the PCR-RFLP method. Comet and buccal micronucleus assays were used to evaluate genetic damage among 115 coal tar workers and 105 control subjects. RESULTS: Both CYP1A1 m1 and CYP1A1 m2 heterozygous and homozygous (wt/mt+mt/mt) variants individually as well as synergistically showed significant association (P<0.05) with genetic damage as measured by tail moment (TM) and buccal micronuclei (BMN) frequencies in control and exposed subjects. CONCLUSION: In our study we found significant association of CYP1A1 m1 and m2 heterozygous (wt/mt) +homozygous (mt/mt) variants with genetic damage suggesting that these polymorphisms may modulate the effects of PAH exposure in occupational settings.

Carcinogenic potencies of polycyclic aromatic hydrocarbons for back-door neighbors of restaurants with cooking emissions.

In the present study, 21 polycyclic aromatic hydrocarbon (PAH) congeners were measured in the exhaust stack of 3 types of restaurants: 9 Chinese, 7 Western, and 4 barbeque (BBQ). The total PAH concentration of BBQ restaurants (58.81 ± 23.89 µg m(-3)) was significantly higher than that of Chinese (20.99 ± 13.67 µg m(-3)) and Western (21.47 ± 11.44 µg m(-3)) restaurants. The total benzo[a]pyrene potency equivalent (B[a]P(eq)) concentrations, however, were highest in Chinese restaurants (1.82 ± 2.24 µg m(-3)), followed by Western (0.86 ± 1.43 µg m(-3), p<0.01) and BBQ-type restaurants (0.59 ± 0.55 µg m(-3), p<0.01). We further developed a probabilistic risk model to assess the incremental lifetime cancer risk (ILCR) for people exposed to carcinogenic PAHs. Because the exhaust stack directly affected the back-door neighbors of these restaurants, we were concerned with the real exposure of groups near the exhaust stack outlets of these restaurants. The ILCRs for total exposure of the neighbors (inhalation+dermal contact+ingestion) were 2.6-31.3, 1.5-14.8, and 1.3-12.2 × 10(-6) in Chinese, Western, and BBQ restaurants, respectively. We suggest that the maximum acceptable exposure time to the exhaust stack outlet area for Chinese, Western, and BBQ restaurants ranges between 5-19, 17-42, and 18-56 h month(-1), respectively, based on an ILCR of less than 10(-6).

Biomarkers of chromosomal damage in peripheral blood lymphocytes induced by polycyclic aromatic hydrocarbons: a meta-analysis.

BACKGROUND: A crucial early event in polycyclic aromatic hydrocarbons (PAHs) carcinogenesis is the induction of genomic instability phenotype that initiates the progression of a proliferative cell into a cancer cell. However, epidemiological results have been inconsistent. OBJECTIVES: To assess reported studies of associations between the levels of chromosomal damage including sister chromatid exchange (SCE), chromosomal aberrations (CA), and cytokinesis-block micronucleus (CBMN) in peripheral blood lymphocytes and occupational exposure to PAHs. METHODS: Meta-analysis on the association between chromosomal damage and occupational exposure to PAHs was performed with STATA 10.0 software package and Review Manager 4.2.10 in this study. RESULTS: We found statistically significant differences in the frequencies of SCE, CBMN, and CA (aberrations per 100 cells) in peripheral blood lymphocytes between PAHs-exposed group and control group, and the summary estimates of weighted mean difference were 1.42 (95% CI: 0.82-2.02), 1.22 (95% CI: 0.33-2.10), and 0.96 (95% CI: 0.37-1.56), respectively. CONCLUSIONS: Data indicate that the frequencies of SCE, CBMN, and CA (aberrations per 100 cells) in peripheral blood lymphocytes might be indicators of early genetic effects for occupationally PAHs-exposed population.

Sources of greater fetal vulnerability to airborne polycyclic aromatic hydrocarbons among African Americans.

BACKGROUND: This study attempted to clarify the household and mother's lifestyle factors that contribute to the greater fetal vulnerability of African-American individuals to airborne polycyclic aromatic hydrocarbons (PAH). METHODS: Non-smoking pregnant women with no known risks of adverse birth outcome were monitored for their personal exposure to airborne PAH. Birth outcomes were collected from the hospital medical record. Modification of the airborne PAH effects was statistically examined. In linear regression analyses, modification of PAH effect by demographic, socioeconomic and behavioural traits on birth weight and fetal growth ratio were respectively tested, adjusting for the gestational age, gender, parity, delivery season, maternal body mass index and weight gained during the present pregnancy. RESULTS: Maternal obesity exacerbated the airborne PAH risk by -491 g per 25th to 80th percentile unit exposure (95% CI -197 to -786 g; p<0.01) among African Americans. In addition, frequent dietary intake of smoked, grilled or barbequed items independently reduced the birth weight of African-American newborns by -204 g (95% CI -21 to -387 g; p=0.03). CONCLUSION: Maternal obesity significantly exacerbated the risk of prenatal PAH exposure in African-American newborns. Also, frequent dietary consumption of PAH-laden food items posed an independent risk on the reduced birth weight among African Americans.

CpG site-specific hypermethylation of p16INK4α in peripheral blood lymphocytes of PAH-exposed workers.

BACKGROUND: Sufficient epidemiologic evidence shows an etiologic link between polycyclic aromatic hydrocarbons (PAH) exposure and lung cancer risk. While the genetic modifications have been found in PAH-exposed population, it is unclear whether gene-specific methylation involves in the process of PAH-associated biologic consequence. METHODS: Sixty-nine PAH-exposed workers and 59 control subjects were recruited. Using bisulfite sequencing, we examined the methylation status of p16(INK4α) promoter in peripheral blood lymphocytes (PBL) from PAH-exposed workers and in benzo(a)pyrene (BaP)-transformed human bronchial epithelial (HBE) cells. The relationships between p16(INK4α) methylation and the level of urinary 1-hydroxypyrene (1-OHP) or the frequency of cytokinesis block micronucleus (CBMN) were analyzed. RESULTS: Compared with the control group, PAH-exposed workers exhibited higher levels of urinary 1-OHP (10.62 vs. 2.52 µg/L), p16(INK4α) methylation (7.95% vs. 1.14% for 22 "hot" CpG sites), and CBMN (7.28% vs. 2.92%) in PBLs. p16(INK4α) hypermethylation in PAH-exposed workers exhibited CpG site specificity. Among the 35 CpG sites we analyzed, 22 were significantly hypermethylated. These 22 hypermethylated CpG sites were positively correlated to levels of urinary 1-OHP and CBMN in PBLs. Moreover, the hypermethylation and suppression of p16 expression was also found in BaP-transformed HBER cells. CONCLUSION: PAH exposure induced CpG site-specific hypermethylation of p16(INK4α) gene. The degree of p16(INK4α) methylation was associated with the levels of DNA damage and internal exposure. IMPACT: p16(INK4α) hypermethylation might be an essential biomarker for the exposure to PAHs and for early diagnosis of cancer.